Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cell Stem Cell. 2022 Dec 1;29(12):1669-1684.e6. doi: 10.1016/j.stem.2022.11.007.
The enthesis, a fibrocartilaginous transition between tendon and bone, is necessary for force transfer from muscle to bone to produce joint motion. The enthesis is prone to injury due to mechanical demands, and it cannot regenerate. A better understanding of how the enthesis develops will lead to more effective therapies to prevent pathology and promote regeneration. Here, we used single-cell RNA sequencing to define the developmental transcriptome of the mouse entheses over postnatal stages. Six resident cell types, including enthesis progenitors and mineralizing chondrocytes, were identified along with their transcription factor regulons and temporal regulation. Following the prior discovery of the necessity of Gli1-lineage cells for mouse enthesis development and healing, we then examined their transcriptomes at single-cell resolution and demonstrated clonogenicity and multipotency of the Gli1-expressing progenitors. Transplantation of Gli1-lineage cells to mouse enthesis injuries improved healing, demonstrating their therapeutic potential for enthesis regeneration.
附着点是肌腱和骨骼之间的纤维软骨过渡区，对于将肌肉产生的力传递到骨骼以产生关节运动是必需的。由于力学需求，附着点容易受伤，而且无法再生。更好地了解附着点的发育过程将导致更有效的治疗方法来预防病理和促进再生。在这里，我们使用单细胞 RNA 测序来定义小鼠附着点在出生后阶段的发育转录组。鉴定了包括附着点祖细胞和矿化软骨细胞在内的六种固有细胞类型，以及它们的转录因子调控子和时间调控。在先前发现 Gli1 谱系细胞对于小鼠附着点发育和修复的必要性之后，我们随后在单细胞分辨率下检查了它们的转录组，并证明了表达 Gli1 的祖细胞具有克隆形成能力和多能性。将 Gli1 谱系细胞移植到小鼠附着点损伤处可改善愈合，证明它们在附着点再生方面具有治疗潜力。
